The broad objectives of this research is to obtain a basic understanding of the mechanisms which govern the functional life-span of the corpus luteum during the menstrual cycle and during early pregnancy in primates. Functional luteolysis in primates cannot be accounted for by a decline in a circulating luteotropic hormone or by the production of a uterine luteolysin. However, relatively small increases in circulating estradiol, achieved experimentally during the luteal phase of the menstrual cycle, induced premature functional regression of the corpus luteum of the rhesus monkey. In addition, the elevation of circulating estrogens, within the physiological range, decreased the responsiveness of the monkey corpus luteum to exogenous human chorionic gonadotropin. This observation has led to the hypotheses that estrogens secreted during the course of the luteal phase of the menstrual cycle and early pregnancy, normally precipitates functional involution of the corpus luteum. Experiments are being conducted to test this hypothesis. The objective of initial studies is to determine the site (ovary, uterus or hypothalamo-hypophysial axis) whereby estrogen acts luteolytically. Once this is accomplished, the mechanism of the luteolytic action of estradiol and the physiological importance of this phenomenon will be examined.